Evidence map›Paper›PMID 35209901›Full record

ArticleCardiovascular diabetology2022

MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes.

Shawn Veitch, Makon-Sébastien Njock, Mark Chandy, M Ahsan Siraj, Lijun Chi, HaoQi Mak, Kai Yu, Kumaragurubaran Rathnakumar, Carmina Anjelica Perez-Romero, Zhiqi Chen and 18 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 2 countries.

Shawn Veitch *Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Makon-Sébastien Njock *Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Mark Chandy *Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
M Ahsan SirajToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Lijun ChiTranslational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
HaoQi MakDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Kai YuToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Kumaragurubaran RathnakumarToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Carmina Anjelica Perez-RomeroTranslational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Zhiqi ChenToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Faisal J AlibhaiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Dakota GustafsonDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Sneha RajuToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Ruilin WuDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Dorrin Zarrin KhatDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Yaxu WangTranslational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Amalia CaballeroTranslational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Patrick MeagherKeenan Biomedical Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Edward LauDepartment of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Lejla PepicStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Henry S ChengDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Natalie J GalantPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Kathryn L HoweToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Ren-Ke LiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Kim A ConnellyTranslational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Mansoor HusainToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Paul Delgado-OlguinStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Jason E FishDepartment of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada. jason.fish@utoronto.ca.ORCID 0000-0003-0640-7277
University Health Network · CAHospital for Sick Children · CACardiovascular Institute of the South · USSt. Michael's Hospital · CAUniversity of Colorado Denver · USUniversity of Toronto · CA

Funding

CIHR PJT148487CIHR PJT149046CIHR PJT162208CIHR PJT173489
6 · The paper itself

Abstract

backgroundType 2 diabetes (T2D) is associated with coronary microvascular dysfunction, which is thought to contribute to compromised diastolic function, ultimately culminating in heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms remain incompletely understood, and no early diagnostics are available. We sought to gain insight into biomarkers and potential mechanisms of microvascular dysfunction in obese mouse (db/db) and lean rat (Goto-Kakizaki) pre-clinical models of T2D-associated diastolic dysfunction.

methodsThe microRNA (miRNA) content of circulating extracellular vesicles (EVs) was assessed in T2D models to identify biomarkers of coronary microvascular dysfunction/rarefaction. The potential source of circulating EV-encapsulated miRNAs was determined, and the mechanisms of induction and the function of candidate miRNAs were assessed in endothelial cells (ECs).

resultsWe found an increase in miR-30d-5p and miR-30e-5p in circulating EVs that coincided with indices of coronary microvascular EC dysfunction (i.e., markers of oxidative stress, DNA damage/senescence) and rarefaction, and preceded echocardiographic evidence of diastolic dysfunction. These miRNAs may serve as biomarkers of coronary microvascular dysfunction as they are upregulated in ECs of the left ventricle of the heart, but not other organs, in db/db mice. Furthermore, the miR-30 family is secreted in EVs from senescent ECs in culture, and ECs with senescent-like characteristics are present in the db/db heart. Assessment of miR-30 target pathways revealed a network of genes involved in fatty acid biosynthesis and metabolism. Over-expression of miR-30e in cultured ECs increased fatty acid β-oxidation and the production of reactive oxygen species and lipid peroxidation, while inhibiting the miR-30 family decreased fatty acid β-oxidation. Additionally, miR-30e over-expression synergized with fatty acid exposure to down-regulate the expression of eNOS, a key regulator of microvascular and cardiomyocyte function. Finally, knock-down of the miR-30 family in db/db mice decreased markers of oxidative stress and DNA damage/senescence in the microvascular endothelium.

conclusionsMiR-30d/e represent early biomarkers and potential therapeutic targets that are indicative of the development of diastolic dysfunction and may reflect altered EC fatty acid metabolism and microvascular dysfunction in the diabetic heart.

Indexed as

Diabetes Mellitus, Type 2Heart FailureMicroRNAsAnimalsBiomarkersEndothelial CellsFatty AcidsMiceRatsStroke VolumeBiomarkersFatty AcidsMicroRNAsMirn30d microRNA, mouseMIRN30 microRNA, ratBiomarkerDiabetesDiastolic dysfunctionEndothelial cellExtracellular vesicleHeart failure with preserved ejection fractionmicroRNAMicrovasculature

Identifiers

PMID35209901
PMCPMC8876371
OpenAlexW4213423229

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.